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Antibiotics
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Pharmacokinetics and Pharmacodynamics Evaluation in the Appropriate Use of Antibacterial...
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Pharmacokinetics and Pharmacodynamics Evaluation in the Appropriate Use of Antibacterial Drugs

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Pharmacokinetics and Pharmacodynamics of Drugs".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 4936

Special Issue Editors

Dr. Soo Min Jang

E-Mail Website
Guest Editor
Department of Pharmacy Practice, Loma Linda University School of Pharmacy, Loma Linda, CA 92350, USA
Interests: kidney diseases; antibiotics; pharmacokinetics; pharmacodynamics; renal replacement therapy
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Jeffrey Lipman

grade E-Mail Website
Co-Guest Editor
1. Jamieson Trauma Institute, Royal Brisbane and Women’s Hospital, Brisbane, QLD 4029, Australia
2. The University of Queensland Centre for Clinical Research, Brisbane, QLD 4029, Australia
Interests: antibiotic administration (particularly pharmacokinetics); pharmacodynamics; clinical trials
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The Antibiotics journal invites academicians, researchers, and clinicians to send abstracts for the Special Issue related to Pharmacokinetics and Pharmacodynamics Evaluations in the Appropriate Use of Antibacterial Drugs.

Over the decades, inappropriate use of antibiotics has caused poor patient outcomes, including antibiotic toxicities and antibiotic resistance. Pharmacokinetics and pharmacodynamics changes in different patient populations (e.g., patients with sepsis) must be accounted for appropriate drug dosing. For example, kidney diseases influence pharmacokinetic parameters such as drug absorption, distribution, transport, and renal and non-renal clearances. Thus, it is critical to inform clinicians how to optimize the selection (antibiotic stewardship) and drug dosing with antibiotics to prevent unnecessary adverse events and poor patient outcomes.

See Antibiotics’Instruction for Authors for guidance on submission policies:
https://www.mdpi.com/journal/antibiotics/instructions

Dr. Soo Min Jang
Prof. Dr. Jeffrey Lipman
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antibiotic stewardship
  • pharmacokinetics
  • pharmacodynamics
  • outcome
  • resistance
  • drug dosing

Published Papers (5 papers)

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Research

13 pages, 1379 KiB  
Article
Pharmacokinetics of Enrofloxacin in Plasma, Urine, and Feces of Donkey (Equus asinus) after a Single Intragastric Administration
by Bowen Yang, Shijie Liu, Jie Cheng, Honglei Qu, Yanxin Guo, Chuanliang Ji, Yantao Wang, Shancang Zhao, Shimeng Huang, Lihong Zhao and Qiugang Ma
Antibiotics 2024, 13(4), 355; https://doi.org/10.3390/antibiotics13040355 - 12 Apr 2024
Viewed by 552
Abstract
Enrofloxacin is a broad-spectrum antimicrobial agent, but the study of its pharmacokinetics/pharmacodynamics (PKs/PDs) in donkeys is rarely reported. The present study aimed to investigate the pharmacokinetics of enrofloxacin administered intragastrically, and to study the pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in plasma, [...] Read more.
Enrofloxacin is a broad-spectrum antimicrobial agent, but the study of its pharmacokinetics/pharmacodynamics (PKs/PDs) in donkeys is rarely reported. The present study aimed to investigate the pharmacokinetics of enrofloxacin administered intragastrically, and to study the pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in plasma, urine, and feces, and the PK/PD parameters were investigated to provide a rationale for enrofloxacin treatment in donkeys. A total of five healthy donkeys were selected for intragastric administration of 7.5 mg·kg−1 BW of enrofloxacin by gavage, and blood, urine, and fecal samples were collected. The results showed that the elimination half-life of plasma enrofloxacin was 11.40 ± 6.40 h, Tmax was 0.55 ± 0.12 h, Cmax was 2.46 ± 0.14 mg·L−1, AUC0–∞ was 10.30 ± 3.37 mg·L−1·h, and mean residence time (MRT) was 7.88 ± 1.26 h. The Tmax of plasma ciprofloxacin was 0.52 ± 0.08 h, Cmax was 0.14 ± 0.03 mg·L−1, and AUC0–∞ was 0.24 ± 0.16 mg·L−1·h. Urinary Cmax was 38.18 ± 8.56 mg·L−1 for enrofloxacin and 15.94 ± 4.15 mg·L−1 for ciprofloxacin. The total enrofloxacin and ciprofloxacin recovered amount in urine was 7.09 ± 2.55% of the dose for 144 h after dosing. The total enrofloxacin and ciprofloxacin recovered amount in feces was 25.73 ± 10.34% of the dose for 144 h after dosing. PK/PD parameters were also examined in this study, based on published MICs. In conclusion, 7.5 mg/kg BW of enrofloxacin administered intragastrically to donkeys was rapidly absorbed, widely distributed, and slowly eliminated in their bodies, and was predicted to be effective against bacteria with MICs < 0.25 mg·L−1. Full article
(This article belongs to the Special Issue Pharmacokinetics and Pharmacodynamics Evaluation in the Appropriate Use of Antibacterial Drugs)
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15 pages, 2994 KiB  
Article
Intrapulmonary and Systemic Pharmacokinetics of Colistin Following Nebulization of Low-Dose Colistimethate Sodium in Patients with Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant Acinetobacter baumannii
by Dong-Hwan Lee, Shin-Young Kim, Yong-Kyun Kim, So-Young Jung, Ji-Hoon Jang, Hang-Jea Jang and Jae-Ha Lee
Antibiotics 2024, 13(3), 258; https://doi.org/10.3390/antibiotics13030258 - 14 Mar 2024
Viewed by 897
Abstract
Colistimethate sodium (CMS) nebulization is associated with reduced systemic toxicity compared to intravenous injection, with potentially enhanced clinical efficacy. This study aimed to assess the pharmacokinetic (PK) properties of colistin during low-dose CMS nebulization in patients with ventilator-associated pneumonia (VAP) caused by carbapenem-resistant [...] Read more.
Colistimethate sodium (CMS) nebulization is associated with reduced systemic toxicity compared to intravenous injection, with potentially enhanced clinical efficacy. This study aimed to assess the pharmacokinetic (PK) properties of colistin during low-dose CMS nebulization in patients with ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii. A nonlinear mixed-effects modeling approach was applied to develop population PK models for colistin in both epithelial lining fluid (ELF) and plasma. Twenty patients participated, and 80 ELF and 100 plasma samples were used for model development. Median colistin concentrations measured in ELF were 614-fold, 408-fold, and 250-fold higher than in plasma at 1, 3, and 5 h, respectively. Time courses in both ELF and plasma were best described by a one-compartment model with a Weibull absorption process. When the final model was simulated, the maximum free concentration and area under the free colistin concentration–time curve at steady state over 24 h in the plasma were approximately 1/90 and 1/50 of the corresponding values in ELF at steady state, respectively. For an A. baumannii MIC of 1 mg/L, inhaling 75 mg of CMS at 6 h intervals was deemed appropriate, with dose adjustments needed for MICs exceeding 2 mg/L. Using a nebulizer for CMS resulted in a notably higher exposure of colistin in the ELF than plasma, indicating the potential of nebulization to reduce systemic toxicity while effectively treating VAP. Full article
(This article belongs to the Special Issue Pharmacokinetics and Pharmacodynamics Evaluation in the Appropriate Use of Antibacterial Drugs)
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11 pages, 1641 KiB  
Article
Relationship between Target Time above Minimum Inhibitory Concentration Achievement Rate of Meropenem Using Monte Carlo Simulation and In-Hospital Survival in Patients with Pseudomonas aeruginosa Bacteremia
by Hajime Nakashima, Motoyasu Miyazaki, Tsuneo Kuwamura, Kazutaka Oda, Yumi Haga and Osamu Imakyure
Antibiotics 2024, 13(3), 219; https://doi.org/10.3390/antibiotics13030219 - 27 Feb 2024
Viewed by 962
Abstract
Pseudomonas aeruginosa bacteremia is associated with a high mortality rate, and meropenem (MEPM) is commonly used to treat it. However, the relationship between the time above the minimum inhibitory concentration (fT>MIC) of MEPM and its therapeutic efficacy in P. [...] Read more.
Pseudomonas aeruginosa bacteremia is associated with a high mortality rate, and meropenem (MEPM) is commonly used to treat it. However, the relationship between the time above the minimum inhibitory concentration (fT>MIC) of MEPM and its therapeutic efficacy in P. aeruginosa bacteremia has not been explored. This study aimed to investigate this relationship by defining the target % fT>MIC of MEPM as 75%. The retrospective study spanned 14 years and included hospitalized patients treated with MEPM for P. aeruginosa bacteremia. Monte Carlo simulation was used to calculate the probability of target attainment (PTA) for each patient, and the threshold for a PTA of 75% fT>MIC associated with in-hospital survival was determined using receiver operating characteristic (ROC) curves. The ROC curve-derived PTA associated with improved in-hospital survival was 65.0%, a significant finding in multivariate logistic regression analysis adjusted for patient background factors (odds ratio: 20.49, 95% confidence interval: 3.02–245.23, p = 0.005). This result suggests a dosing regimen that achieves a PTA of at least 65% when the target fT>MIC of MEPM for treating P. aeruginosa bacteremia is defined as 75%. Full article
(This article belongs to the Special Issue Pharmacokinetics and Pharmacodynamics Evaluation in the Appropriate Use of Antibacterial Drugs)
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13 pages, 1646 KiB  
Article
In Vitro Antibacterial Activity of Ceftobiprole and Comparator Compounds against Nation-Wide Bloodstream Isolates and Different Sequence Types of MRSA
by Lingqin Li, Wangxiao Zhou, Yunbo Chen, Ping Shen and Yonghong Xiao
Antibiotics 2024, 13(2), 165; https://doi.org/10.3390/antibiotics13020165 - 07 Feb 2024
Viewed by 1181
Abstract
Bloodstream infections by bacteria, especially multidrug-resistant bacteria, remain a worldwide public health concern. We evaluated the antibacterial activity of ceftobiprole and comparable drugs against different bloodstream isolates and different sequence types of methicillin-resistant Staphylococcus aureus (MRSA) in China. We found that MRSA, methicillin-susceptible Staphylococcus [...] Read more.
Bloodstream infections by bacteria, especially multidrug-resistant bacteria, remain a worldwide public health concern. We evaluated the antibacterial activity of ceftobiprole and comparable drugs against different bloodstream isolates and different sequence types of methicillin-resistant Staphylococcus aureus (MRSA) in China. We found that MRSA, methicillin-susceptible Staphylococcus aureus (MSSA), and methicillin-susceptible coagulase-negative Staphylococcus (MSCNS) displayed ceftobiprole sensitivity rates of >95%, which are similar to the rates for linezolid, daptomycin, and vancomycin. Of the tested MRCNS strains, 90.4% were sensitive to ceftobiprole. The sensitivities of ST59, ST398, and ST22 MRSA to ceftobiprole were higher than that of ST239. Ceftobiprole’s MIC50/90 value against Enterococcus faecalis was 0.25/2 mg/L, whereas Enterococcus faecium was completely resistant to this drug. Ceftobiprole exhibited no activity against ESBL-positive Enterobacterales, with resistance rates between 78.6% and 100%. For ESBL-negative Enterobacterales, excluding Klebsiella oxytoca, the sensitivity to ceftobiprole was comparable to that of ceftazidime, ceftriaxone, and cefepime. The MIC50/90 value of ceftobiprole against Pseudomonas aeruginosa was 2/16 mg/L, and for Acinetobacter baumannii, it was 32/>32 mg/L. Thus, ceftobiprole shows excellent antimicrobial activity against ESBL-negative Enterobacterales and Pseudomonas aeruginosa (comparable to that of ceftazidime, ceftriaxone, and cefepime); however, it is not effective against ESBL-positive Enterobacterales and Acinetobacter baumannii. These results provide important information to clinicians. Full article
(This article belongs to the Special Issue Pharmacokinetics and Pharmacodynamics Evaluation in the Appropriate Use of Antibacterial Drugs)
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13 pages, 3059 KiB  
Article
Endotoxin-Induced Sepsis on Ceftriaxone-Treated Rats’ Ventilatory Mechanics and Pharmacokinetics
by Juliana Savioli Simões, Rafaela Figueiredo Rodrigues, Bruno Zavan, Ricardo Murilo Pereira Emídio, Roseli Soncini and Vanessa Bergamin Boralli
Antibiotics 2024, 13(1), 83; https://doi.org/10.3390/antibiotics13010083 - 15 Jan 2024
Viewed by 954
Abstract
Sepsis can trigger acute respiratory distress syndrome (ARDS), which can lead to a series of physiological changes, modifying the effectiveness of therapy and culminating in death. For all experiments, male Wistar rats (200–250 g) were split into the following groups: control and sepsis-induced [...] Read more.
Sepsis can trigger acute respiratory distress syndrome (ARDS), which can lead to a series of physiological changes, modifying the effectiveness of therapy and culminating in death. For all experiments, male Wistar rats (200–250 g) were split into the following groups: control and sepsis-induced by endotoxin lipopolysaccharide (LPS); the control group received only intraperitoneal saline or saline + CEF while the treated groups received ceftriaxone (CEF) (100 mg/kg) IP; previously or not with sepsis induction by LPS (1 mg/kg) IP. We evaluated respiratory mechanics, and alveolar bronchial lavage was collected for nitrite and vascular endothelial growth factor (VEGF) quantification and cell evaluation. For pharmacokinetic evaluation, two groups received ceftriaxone, one already exposed to LPS. Respiratory mechanics shows a decrease in total airway resistance, dissipation of viscous energy, and elastance of lung tissues in all sepsis-induced groups compared to the control group. VEGF and NOx values were higher in sepsis animals compared to the control group, and ceftriaxone was able to reduce both parameters. The pharmacokinetic parameters for ceftriaxone, such as bioavailability, absorption, and terminal half-life, were smaller in the sepsis-induced group than in the control group since clearance was higher in septic animals. Despite the pharmacokinetic changes, ceftriaxone showed a reduction in resistance in the airways. In addition, CEF lowers nitrite levels in the lungs and acts on their adverse effects, reflecting pharmacological therapy of the disease. Full article
(This article belongs to the Special Issue Pharmacokinetics and Pharmacodynamics Evaluation in the Appropriate Use of Antibacterial Drugs)
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